An aminoadamantyl carbamate derivative is a useful compound as a pharmaceutical synthesis material or an intermediate. For example, the derivative can be used as a synthetic intermediate of a compound represented by the Formula (VIII):
its salt, or a solvate thereof.
The compound represented by the Formula (VIII) has 11βHSD-1 inhibitory activity, and a pharmaceutical composition comprising the compound is known to be useful as a therapeutic agent for type II diabetes (Patent Document 1 and Patent Document 2).
Non Patent Document 1 describes a process for producing 1-hydroxy-4-aminoadamantane by a reaction such as Leuckart reaction from 1-hydroxy-4-adamantanone. The document states that, in the reaction, the ratio of the produced stereoisomer is advantageous for syn isomer, where the ratio of the amount of syn isomer produced to the amount of anti isomer produced is from 3:1 to 1:1.
Non Patent Document 2 describes a process for producing 1-hydroxy-4-aminoadamantane by performing hydroxylation of 2-aminoadamantane in a 1:10 mixture of nitric acid and sulfuric acid.
Entry 6 in Table 1 of Non Patent Document 3 describes a process of reacting 5-hydroxy-2-adamantanone with benzylamine in the presence of H2/5% Pt—C, and states that the ratio of the stereoisomer produced in the reaction, i.e. the amount of anti isomer produced to the amount of syn isomer produced is 1:1. Moreover, Entry 8 in Table 2 states that the ratio of the amount of anti isomer produced to the amount of syn isomer produced of 2.7:1 can be obtained by reacting 5-hydroxy-2-adamantanone with benzylamine in the presence of H2/5% Rh—C and Al (iOPr)3. The production ratios of anti isomer to syn isomer in these two experimental examples were measured by 1H-NMR, and neither of the compounds was isolated.
Patent Document 3 describes a process for producing an anti isomer of 1-hydroxy-4-aminoadamantane, the process comprising reacting 5-hydroxy-2-adamantanone with L(−)-1-phenyl-ethylamine in the presence of a heterogeneous catalyst, for example, rhodium supported by carbon, purifying the resulting mixture of anti isomer and syn isomer with column chromatography, isolating the anti isomer and then debenzylating the anti isomer.
Patent Document 4 describes a process for producing an anti isomer, the process comprising reacting 5-hydroxy-2-adamantanone with ammonia/methanol in the presence of sodium borohydride, amidating the resulting mixture of anti isomer and syn isomer, and purifying the resulting amide body with column chromatography.
Patent Document 5 describes a process for producing an anti isomer, the process comprising amidating a mixture of anti isomer and syn isomer of 1-hydroxy-4-aminoadamantane with carboxylic acid and purifying the resulting amide body with column chromatography.
However, none of the documents describe a process for preparing an aminoadamantyl carbamate derivative and a compound represented by the Formula (VIII) using the above derivative. Moreover, in the process described in any of the documents, the produced mixture of anti isomer and syn isomer needed to be purified with column chromatography, and thus the process was industrially difficult to apply.
Patent Document 6 describes a process for producing 1-hydroxy-4-aminoadamantane, the process comprising setting 5-hydroxy-2-adamantanone and benzylamine derivative to a reductive aminating reaction, obtaining preferentially an anti isomer by crystallization purification from the produced mixture of anti isomer and syn isomer, followed by deprotection. The document states that the ratio of the amount of anti isomer to the amount of syn isomer of the 1-hydroxy-4-aminoadamantane produced by the process is from 13:1 to 50:1. However, the document does not describe a process for preparing an aminoadamantyl carbamate derivative of the present invention and a compound represented by the Formula (VIII) using the above derivative.